The purpose of this research is the investigation of the role mycoplasmas may play in rheumatoid arthritis by study of a rheumatoid- like arthritic disease produced in the mouse by intravenous inoculation of Mycoplasma pulmonis. We have previously shown 1) serological reactivity between M. pulmonis and mouse synovial membrane, 2) development of cellular hypersensitivity to normal mouse synovium, and 3) that after the 4th week of infection no correlation between the presence of mycoplasmas and the extent of disease exists. Our present goal is to attempt to separate the direct damage done by the microorganism from the secondary immunological events, and to attempt to identify the role of each in the pathophysiology of the disease. To this end we intend to 1) examine possible cell-mediated immune cross- reactivity between synovial and mycoplasmal antigens using the antigen dependency of migration inhibition factor (MIF) activity; 2) examine synovial tissue from arthritic animals of various ages to look for persistent mycoplasma antigen and possible immune complexes bound to synovium; 3) attempt to transfer the disease by cellular means, using either lymphocytes from arthritic animals or parabiosis of arthritic to normal mice; 4) treat mice with antibiotics and immunosuppressives separately to evaluate their individual roles; and 5) attempt to assess lymphotoxin mediated damage to tissue culture lines by addition of tissue and mycoplasma antigens and complexes.